D2-40, Podoplanin, and CD31 as a Prognostic Predictor in Invasive Ductal Carcinomas of the Breast

Purpose: Distant metastasis and recurrence are major prognostic factors associated with breast cancer. Both lymphovascular invasion (LVI) and blood vessel invasion (BVI) are important routes for metastasis to regional lymph nodes and for systemic metastasis. Despite the importance of vascular invasion as a prognostic factor, application of vascular invasion as a histopathological criterion is controversial. The aim of this study was to distinguish LVI from BVI in prognosis and recurrence of breast cancer using an endothelial subtype specific immunohistochemical stain (podoplanin, D2-40, and CD31). Methods: Sections from 80 paraffin-embedded archival specimens of invasive breast cancer were stained for podoplanin, D2-40, or CD31 expression. Immunohistochemical staining results were correlated with clinicopathological features, such as tumor size, status of lymph node metastases, estrogen receptor status, progesterone receptor status, human epidermal growth factor receptor-2 expression, and recurrence. Patients with ductal carcinoma in situ and stage IV breast cancer were excluded. Results: A significant correlation was found between D2-40 LVI positivity and lymph node metastasis (p = 0.022). We found a significant correlation between D2-40 LVI positivity and recurrence of breast cancer (p = 0.014). However, no significant correlation was found between BVI and recurrence. A poorer disease free survival was shown for D2-40 positive LVI (p = 0.003). In a multivariate analysis, the presence of D2-40 LVI positivity revealed a significant association with decreased disease-free survival. Conclusion: D2-40 LVI positivity was a more prognostic predictor of breast cancer than BVI.